Research: Studies over recent years revealed that an enhancement of brown adipose tissue activity can correct hyperlipidemia and prevent diet induced obesity and its harmful metabolic consequences. It has widely been assumed that all classical brown adipocytes in brown fat were functionally similar. This application is based on a recent unpublished discovery by Dr. Wang that there are two new, distinct, populations of classical brown adipocytes co-existing in normal brown fat that display distinct transcriptional fingerprints and morphology. The hypothesis is that they are active highly thermogenic and the resting low thermogenic brown adipocytes. This project will explore the function, dynamic and regulation of this two brown adipocyte subpopulations during development and under environmental and physiology challenges such as cold exposure and high fat diet feeding. By figuring out the key regulatory pathways leading to the diversity between the two subpopulations of brown adipocytes, we can identify the potential pharmaceutical targets to induce inter-conversion of brown adipocytes from low thermogenic capability to high thermogenic capability. Meanwhile, the proposed research will also investigate when the two subpopulations diverse during maturation; as well as how high fat diet challenge impairs the inter-conversion of the two subpopulations. In summary, the proposed research will unmask the complex physiology of brown adipose tissue, which is essential to improve our ability to identify the potential most effective therapeutic approaches against obesity and type II diabetes. Career goals: Dr. Wang's ultimate career goal as a biological scientist is to have her own productive academic lab devoted to metabolism research focusing on the pathogenesis and treatment of obesity, type 2 diabetes and the related metabolic syndromes. To be able to establish her independent research program, her immediate career objectives in the reward period are to: 1) Learn new techniques and knowledge in the field of developmental and cell biology. 2) Acquire new knowledge and expertise in developmental and cell biology, a direction different from her current mentor. 3) Further practice the skills for writing and publishing manuscripts by publishing more research articles. 4) Expand her network of colleagues for potential well-suited job offers and future collaborations. 5) Establish an independent funding record for my future funding applications. Career development plan: During the award period, Wang will strengthen her effectiveness in the above key career objectives through constant interactions with her mentor Dr. Philipp Scherer and collaborators Drs. Sean Morrison, Ralph DeBerardinis and Rana Gupta. She will also complete several courses provided by UTSW to prepare her for the independence.